RhD negative women transfused RhD positive blood: Alloimmunization prophylaxis protocol and experiences

2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S161-S161
Author(s):  
R Alkhateb ◽  
V Prajapati ◽  
J Daniels ◽  
L Greebon
Keyword(s):  
Post Treatment ◽  
High Dose ◽  
Red Cell ◽  
Inclusion Criteria ◽  
Total Blood ◽  
Significant Drop ◽  
To Receive ◽  
Hospital Protocol

Abstract Introduction/Objective Preventing allomiunization from D-mismatched transfusions, i.e., transfusion RhD positive (RhD+) red blood cells (RBC) to an RhD negative (RhD–) individual, is not well established. We describe our hospital protocol and experiences managing RhD– young women who received emergency release D-mismatched transfusions. Methods/Case Report The pathologists evaluate all patients who received D-mismatched blood transfusions. The inclusion criteria for alloimmunization prophylaxis protocol include: RhD– females; <50 years old; No current or historical Anti-D; and received ≥1 unit of RhD+ blood. The prophylaxis protocol depends on the RBC volume (RBCV) transfused. Patients who receive RBCV <20% of their total blood volume (TBV) are eligible to receive high dose RhIg, calculated based on the volume transfused. Those who received RBCV ≥20% of TBV would be eligible for red cell exchange (RBCX) followed by RhIg. Results (if a Case Study enter NA) Since 2016, four eligible patients received RhIg prophylaxis protocol and none met the criteria for RBCX. All the patients started the prophylaxis protocol within 24 hours of transfusion and completed it within 72 hours. One patient developed post treatment hemolysis and significant drop in hemoglobin requiring blood transfusion. Passive anti-D post treatment was confirmed in three patients, and one had passive anti C. Three of the four patients had follow up antibody screens >6 months post treatment that were negative for RhD alloimmunization. Conclusion Our therapeutic plan, the first well established protocol, involves identifying eligible patients based on set criteria and protocols. Our experience demonstrates that this protocol is effective in reducing/preventing RhD alloimmunization.

DHA supplementation in infants born preterm and the effect on attention at 18 months’ corrected age: follow-up of a subset of the N3RO randomised controlled trial

2020 ◽  
pp. 1-12 ◽  
Author(s):  
Erandi Hewawasam ◽  
Carmel T. Collins ◽  
Beverly S. Muhlhausler ◽  
Lisa N. Yelland ◽  
Lisa G. Smithers ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Primary Outcome ◽  
Controlled Trial ◽  
High Dose ◽  
Peak Period ◽  
Soya Oil ◽  
Randomised Controlled ◽  
To Receive ◽  
The Brain

Abstract Infants born preterm miss out on the peak period of in utero DHA accretion to the brain during the last trimester of pregnancy which is hypothesised to contribute to the increased prevalence of neurodevelopmental deficits in this population. This study aimed to determine whether DHA supplementation in infants born preterm improves attention at 18 months’ corrected age. This is a follow-up of a subset of infants who participated in the N3RO randomised controlled trial. Infants were randomised to receive an enteral emulsion of high-dose DHA (60 mg/kg per d) or no DHA (soya oil – control) from within the first days of birth until 36 weeks’ post-menstrual age. The assessment of attention involved three tasks requiring the child to maintain attention on toy/s in either the presence or absence of competition or a distractor. The primary outcome was the child’s latency of distractibility when attention was focused on a toy. The primary outcome was available for seventy-three of the 120 infants that were eligible to participate. There was no evidence of a difference between groups in the latency of distractibility (adjusted mean difference: 0·08 s, 95 % CI –0·81, 0·97; P = 0·86). Enteral DHA supplementation did not result in improved attention in infants born preterm at 18 months’ corrected age.

Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.

1985 ◽  
Vol 3 (2) ◽  
pp. 176-183 ◽  
Author(s):  
H M Dhingra ◽  
M Valdivieso ◽  
D T Carr ◽  
D F Chiuten ◽  
P Farha ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
To Receive

One hundred sixty-seven evaluable patients with non-small-cell lung cancer were randomized to receive high-dose cisplatin and vindesine (PVD), or cisplatin and VP-16-213 (etoposide epipodophyllotoxin) (PVP), or cisplatin with VP-16-213 and vindesine (PVPVD). The patient distribution and characteristics were similar in all the treatment arms. The response rate differences (35% in PVD arm, 30% in PVP arm, and 22% in PVPVD arm) were not statistically significant (P = .33). Response durations were 43 weeks in the PVD arm, 20 weeks in the PVP arm, and 27 weeks in the PVPVD arm. Median survival was 29 weeks in the PVD and PVP arms and 28 weeks in the PVPVD arm. Median survival time of responding patients was 76 weeks in the PVD arm and 65 weeks in the PVP arm; 78% of patients were alive at 22+ to 87+ weeks follow-up in the PVPVD arm. Myelosuppression was similar in all three treatment arms. Significantly more azotemia occurred in the PVD arm than in the PVP and PVPVD arms (P = .002), and significantly more neuropathy in the PVD and PVPVD arms than in the PVP arm (P = .003 and .005). All the treatment arms have similar antitumor activity in non-small-cell lung cancer, but the PVP combination is slightly less toxic than the PVD and PVPVD treatment arms.

Evaluation of intensive postremission chemotherapy for adults with acute nonlymphocytic leukemia using high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide.

1987 ◽  
Vol 5 (6) ◽  
pp. 918-926 ◽  
Author(s):  
M S Tallman ◽  
F R Appelbaum ◽  
D Amos ◽  
R S Goldberg ◽  
R B Livingston ◽  
...  
Keyword(s):  
Cytosine Arabinoside ◽  
Disease Free Survival ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Survival ◽  
Kaplan Meier ◽  
To Receive ◽  
Disease Free ◽  
Historical Controls

In order to test the toxicity and efficacy of intensive postremission therapy with high-dose cytosine arabinoside with L-asparaginase and amsacrine with etoposide in adults with acute nonlymphocytic leukemia (ANL), 100 adults (ages 19 to 75) with previously untreated ANL were entered into a study using six sequential cycles of chemotherapy. Cycles 1 (induction), 3, and 5 included conventional doses of daunomycin, cytosine arabinoside, 6-thioguanine, vincristine (VCR), and prednisone. Cycle 2 was cytosine arabinoside 3 g/m2 intravenously (IV) every 12 hours for four doses, followed by L-asparaginase 10,000 U intramuscularly (IM) at hour 42; this combination was repeated 1 week later. Cycle 4 included amsacrine 120 mg/m2/d and etoposide 100 mg/m2/d, both IV for five days, and cycle 6 was three monthly courses of VCR on day 1, and prednisone, mercaptopurine, and methotrexate each for five days. Seventy-four patients (74%) achieved complete remission (CR) (51 with cycle 1 and 23 after cycle 2). The overall disease-free survival (DFS) for patients achieving CR is 27% at 3 years by Kaplan-Meier analysis, while for patients achieving CR with cycle 1 it is 34%. The actuarial probability of being free from relapse at 3 years for patients achieving CR is 34%. Sixteen of the 74 CR patients (22%) died in CR while continuing to receive intensive chemotherapy, including 12 (18%) who succumbed to infection (nine bacterial, three fungal). After a median follow-up of 20 months, 36 patients have relapsed and 21 remain alive in CR. Intensive consolidation with high-dose cytosine arabinoside, amsacrine, and etoposide can modestly prolong DFS compared with historical controls. However, relapse continued to be a major problem and, in addition, with more aggressive consolidation therapy, infection during marrow aplasia resulted in a significant number of deaths.

scholarly journals Retrospective and Prospective Study of Childhood Autoimmune Hemolytic Anemia. a Preliminary Report from the Red Cell Working Group of the Paediatric Hemato-Oncology Italian Associations (AIEOP)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 947-947
Author(s):  
Saverio Ladogana ◽  
Raffaella Colombatti ◽  
Silverio Perrotta ◽  
Angela Maggio ◽  
Matteo Maruzzi ◽  
...  
Keyword(s):  
Partial Response ◽  
Prospective Study ◽  
Autoimmune Hemolytic Anemia ◽  
Complete Response ◽  
High Dose ◽  
Red Cell ◽  
Line Treatment ◽  
Secondary Form ◽  
Hb Concentration

Autoimmune hemolytic anemia (AIHA) is an uncommon disease of childhood caused by the premature destruction of erythrocytes by autoantibodies. In this rare disease both diagnostic criteria and therapeutic approaches are not well standardized. The Red Cell Working Group of the Pediatric Italian Hematogy and Oncology Association (AIEOP) developed specific recommendations to help Physicians for AIHA management. The document is available on the AIEOP website since November 1st 2013. The Italian Pediatric AIHA Group began an observational, retrospective and prospective study in order to monitor the management of children with AIHA diagnosed from 2010 to 2018, and to assess whether the availability of AIEOP recommendations had an impact on the clinical management of such patients in AIEOP Centers. We collected a national cohort of 159 children with AIHA from 21 AIEOP Centers; 48 patients were diagnosed before November 2013 and 111 patients after that date. Gender was 56% males and 44% females; median age at diagnosis was 47 months, with 11.9% under 12 months of age; 8.2% of children were born prematurely and 3.9% showed congenital malformations. 23.2 % of patients had a familiar history of immunological, hematological or oncological diseases. The median hemoglobin level at diagnosis was 6.1 gr/dL. Table 1 reports the distribution of our cases, according to the different type of autoantibodies. The comparison between the retrospective and prospective study did not reveal significative differences in clinical and biological presentation. The cold IgM forms were mainly post infective (38.4%) or primary forms (53.8%), only one patient had a secondary form due to a primitive immunodeficiency. These patients did not develop other diseases during follow up (median follow up: 28,6 months). The preliminary results of treatment and follow up of the 146 patients with warm antibody AIHA revealed the following: The treatment with conventional dose of steroids (median dose 2 mg/Kg, range 0.7- 3.5 mg/Kg) was started in 94.4% of patients, in 53% of cases on the same day of diagnosis. A high number of children used additional treatment: red blood cell transfusions (51.4%), high dose Prednisolone (59.7%), high dose i.v. Immunoglobulin (49.7%) and Plasma Exchange (1.4%). 9.5% of patients, with poor responsive disease, needed alternative drugs during the first four weeks of therapy. Response criteria were so defined: a complete response was defined as the achievement of an Hb concentration greater than or equal to the lower normal limit for age with no signs of haemolysis, i.e. normal reticulocyte count and bilirubine concentration. A partial response was defined as an increase of Hb >2 g/dL without the Hb concentration reaching a normal value for the patient age and no response as an increase of Hb< 2 g/dL and/or dependence on transfusion. A complete response was reached by 62.5%, 79.3%, 85.1% at 3, 4, 6 weeks respectively. 14.9% of patients had either a partial response or a resistant disease at 6 weeks. IgG/IgG+C3d positivity was a negative prognostic factor, as compared to positivity to C3d only, with the need of a second line treatment (prevalently Mabthera or Mycophenolate Mofetil) in 31.7% vs 0, respectively (p 0.009). Currently 6.1% of the patients were lost to follow up, 1.3% died, 55,8% are in Complete Response without events and 21.9% of the patients are still on treatment . At the last follow up, in the whole "cohort" of warm AIHA, 58% have a Primary form, 15.7% an isolated post infective form and 27.7% a Secondary form (56% Evans Syndrome). The management of the patients diagnosed after November 2013 was mostly in agreement with our recommendations, whose comprehensive therapeutic algorithm is reported in table 2, with prolonged steroid tapering in order to extend the treatment for at least 6 months. The most important difference between the retrospective and prospective study was the duration of first line treatment: 6 months or more, for steroid dependence, in 71.6% of patients in the prospective study versus 52.3% of the retrospective (p 0.031) and, more importantly, the percentage of relapsed patients: 8.3% in the prospective study versus 29.8% of the retrospective (p 0.001), these data need a longer follow up (median follow up: 24 months in the prospective study versus 63 in the retrospective) Disclosures Colombatti: Global Blood Therapeutics: Consultancy; Novartis: Consultancy; AddMedica: Consultancy.

Sustained Effect of First Line Sequential Therapy with Intensive Consolidation Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) after Reduced Intensity Conditioning (RIC) for Patients with Acute Myeloblastic Leukemia (AML) in First Complete Remission (CR1).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3000-3000
Author(s):  
Didier Blaise ◽  
R. Tabrizi ◽  
C. Faucher ◽  
Mohamad Mohty ◽  
J.O. Bay ◽  
...  
Keyword(s):  
High Risk ◽  
Cumulative Incidence ◽  
Sequential Therapy ◽  
High Dose ◽  
Intensive Chemotherapy ◽  
Consolidation Chemotherapy ◽  
Hematopoietic Stem ◽  
Cell Counts ◽  
To Receive

Abstract We recently reported our experience using RIC prior to ASCT in pts with AML in CR1 (Blaise, Cancer, 2005). We have shown that RIC-based ASCT can be safely used in this setting after intensive consolidation chemotherapy. With a median follow-up of 18 months, disease control was high and was not related to a selection bias (Mohty, Leukemia, 2005). In the present analysis, we investigated if this control was maintained after a longer follow-up. Thirty-seven pts (age: 51 (range, 26–60)) with high risk clinical characteristics (n=26; 70%) (Age ≥ 50 (N=22, 59%); Associated severe comorbidity (N=10; 30%)) and/or poor risk leukemic features (n=24; 65%) (Poor Cytogenetics (N=13, 35%); failure of first induction course (N= 10, 27%); secondary leukemia (N= 4; 11%), High white blood cell counts(N= 5; 14%) or partial remission (N=1, 3%)) were included in this analysis. After CR1, all pts received a low dose cytarabine consolidation chemotherapy followed one month later by one course of high dose cytarabine (24 g/m²) and anthracycline (HIDAC). Pts were then scheduled to receive ASCT prepared with RIC (fludarabine (180 mg/m²), busulfan (8 mg/kg), Thymoglobulin (2.5 to 10 mg/kg)) followed with BMT (N=10 (28%) or PBSC (N=26 (72%)). However after treating the first pts, it becomes evident that this schedule was not associated prohibitory toxicity. All following pts were, thus, proposed to receive one month after HIDAC, one course of melphalan (140 mg/m²) (HDMEL) with auto-SCT followed after recovery by the allo-SCT. Overall, 21 pts received HIDAC only and 16 HIDAC and HDMEL. Median follow-up at time of abstract is 3 years (16 months–70 months). 15 pts experienced aGVHD (Grade 1: 7; Grade 2: 4; Grade 3–4: 4). The cumulative incidence of grade 2–4 aGVHD was 22% (9–35). 33 pts (90%) were evaluable for cGVHD: 10 and 14 pts presented a limited and extensive form respectively. The cumulative incidence of cGVHD was 65 % (50–80). Three deaths were attributed to non-relapse causes (AGVHD: 1; CGVHD: 2° (cumulative incidence of non-relapse death (NRD): 8% (95% CI: 0–17). In all, 8 pts relapsed at 5 months (2–19) (cumulative incidence: 22% (95% CI, 9–35). Relapse was clearly associated with the absence of cGVHD (cGVHD: 4 (4–12), no cGVHD 44% (12–76), p=.02) and at a lesser extent with the intensity of consolidation chemotherapy (HIDAC: 33% (13–53); HIDAC + AUTO; 6% (0–19%), p=.06). Twenty-six pts are still alive in CR1 for overall survival and leukemia-free survival (LFS) probability estimates at 4 years of 67 % (95%CI, 49–81%) and 68% (95%CI, 50–81%) respectively. When restricting the analysis to the 33 pts evaluable for cGVHD, cGVHD remained the only independent risk factor positively influencing LFS (cGVHD: 83% (59–74); no cGVHD (56% (27–81), p=.03). We conclude that RIC Allo-SCT preceded by adequate prior intensive chemotherapy might offer a relatively low NRD while exerting a sustained leukemia control even in high risk pts. The intensity of intensive chemotherapy needed for optimal will be assessed prospectively.

Phase III Trial of Immunotherapy with Recombinant Interleukin-2 (rIL-2) Versus Observation in Patients < 60 Years with Acute Myeloid Leukemia (AML) in First Remission (CR1): Preliminary Results from Cancer and Leukemia Group B (CALGB) 19808.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 157-157 ◽  
Author(s):  
Jonathan E. Kolitz ◽  
Vera Hars ◽  
Daniel J. DeAngelo ◽  
Steven L. Allen ◽  
Thomas C. Shea ◽  
...  
Keyword(s):  
Survival Rate ◽  
Interleukin 2 ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Cross Resistance ◽  
High Dose ◽  
Phase Iii Trial ◽  
Effector Cells ◽  
To Receive

Abstract The CALGB evaluated the use of rIL-2 for immunotherapy of minimal residual disease in a phase III trial in patients with AML in first CR after completing all planned chemotherapy. The rationale supporting the use of rIL-2 in this setting includes its ability to effect antigen-independent cytotoxicity against AML blasts, its non-cross resistance with cytotoxic agents, and its ability to expand cytotoxic T and natural killer (NK) cells. Pts &lt; 60 years with untreated non-M3 AML were eligible. 734 patients were enrolled. The first 302 patients were randomized between 2 induction regimens: Ara-C, Daunorubicin, and Etoposide (ADE) or ADEP with the P-glycoprotein modulator PSC-833 (Kolitz et al, ASH 2005). The remaining 432 patients received ADE induction. Post-remission therapy was based on cytogenetic risk factors: patients with Core Binding Factor (CBF) AML received 3 courses of High-Dose Ara-C (HiDAC), while all others were assigned to receive a 2 step autologous transplant (ASCT) regimen (Linker et al, Biol Blood Marrow Transpl 2000). Randomization between rIL-2 and observation was to occur no later than 120 days after day 1 of the last HiDAC cycle or day 0 of ASCT, as soon as the neutrophil count &gt; 750/μl, platelets &gt; 50,000/μl with bone marrow showing a leukemia-free state and trilineage maturation and recovery from non-hematological toxicity to &lt; grade 2. The 90 day immunotherapy regimen consisted of low-dose rIL-2 sequences for expanding cytotoxic effector cells and brief, higher dose bolus treatments aimed at activating them. rIL-2 was given SC at 1 x 106 IU/m2 on days 1–14, 19–28, 33–42, 47–56, 61–70 and 75–90, and 12–15 x 106 IU/m2 on days 15–17, 29–31, 43–45, 57–59 and 71–73. CR was achieved in 77% of evaluable patients. After HiDAC consolidation or ASCT, patient refusal, early relapse, and delayed blood count recovery accounted for nearly all failures to undergo randomization to IL-2 or observation. The distribution of patients with CBF and non-CBF AML was comparable between the randomized arms. The median follow-up time from the post-remission randomization date for the surviving patients is 29 months. By intention-to-treat, for the 214 randomized patients, the 3-year disease-free survival rate is 45% (95% CI: 35%, 56%) on the observation arm and 56% (47%, 67%) on the rIL-2 arm (p=0.11; logrank test); the 3-year overall survival rate is 61% (52%, 72%) for patients randomized to observation and 68% (58%, 79%) for the rIL-2 arm (p=.0.09). Twenty-nine of the 107 patients randomized to rIL-2 therapy either refused to receive rIL-2 or were unable to start because of unresolved toxicities; another 28 patients started treatment but failed to complete their 90-day course. Grade 4 toxicities were neutropenia (17%), thrombocytopenia (11%), febrile neutropenia (FN, 1%), increased bilirubin (1%) and hypocalcemia (1%). Grade 3 toxicities, observed in 10%–14% of patients, were hypotension, fatigue, dehydration and FN. We conclude that post-consolidation immunotherapy with 90 days of rIL-2 is tolerable but not well accepted by patients and/or physicians. Further follow-up and additional analyses are planned, correlating outcomes with clinical subsets, amount of rIL-2 therapy received, as well as measurements of ex vivo cytotoxicity mediated by patients’ effector cells against cryopreserved autologous AML blasts.

Patterns of Hypomethylating Agent and Transfusion Use in Myelodysplastic Syndrome: a Claims Database Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2490-2490
Author(s):  
Hind T Hatoum ◽  
Swu-Jane Lin ◽  
Deborah Buchner ◽  
Edward Kim
Keyword(s):  
Logistic Regression ◽  
Myelodysplastic Syndrome ◽  
Poisson Regression ◽  
Research Funding ◽  
Myelogenous Leukemia ◽  
Transfusion Rate ◽  
Inclusion Criteria ◽  
Significant Difference ◽  
To Receive

Abstract Abstract 2490 Poster Board II-467 Introduction: Myelodysplastic syndrome (MDS) is characterized by ineffective hematopoiesis, multilineage dysplasia, peripheral cytopenias, and susceptibility to leukemic transformation. Supportive treatments include red blood cell (RBC) and platelet (PLT) transfusions as well as erythrocyte stimulating agents (ESAs) to correct disease-induced cytopenias. Active treatment with hypomethylating agents (HMAs) have been shown in clinical trials to reduce transfusion dependence and leukemic progression among patients with MDS. The purpose of this study is to describe the patterns of care among patients with MDS, and outcomes associated with HMA treatment options. Methods: Data were obtained from the MarketScan® database, which contains pharmacy, medical, hospital, and laboratory claims for several million members, from January 2002 through June 2008. Inclusion criteria included: age 18 or older; at least 2 claims with an ICD-9 diagnosis of MDS in 2006 or later; at least 6 months of pre-diagnosis health plan enrollment; at least 4 months of enrollment after initial HMA treatment; at least 1 complete cycle of decitabine (DAC; 5 treatments) or azacitidine (AZA, 7 treatments). Patients were excluded if they were treated with lenalidomide, had a prior cancer diagnosis, prior treatment with DAC or AZA, or had other isolated cytopenia or myeloproliferative diagnoses. Patients with a diagnosis of acute myelogenous leukemia within the first 28 days of treatment were also excluded. Descriptive statistics characterized patient demographics, including time between diagnosis and treatment, days per cycle, use of ESA, and number of treatment cycles. Logistic regression assessed predictors of HMA treatment using age at MDS diagnosis, gender, Charlson Comorbidity Index (CCI), and calendar year as predictors. Poisson regression compared the risk of RBC or PLT transfusion between DAC and AZA, controlling for age, gender, CCI, treatment cycles, time to initiating treatment, and follow-up duration. Results: 2525 patients met full inclusion criteria (51% female), of whom 95.4% received no HMA treatment. Logistic regression revealed that females were less likely to receive HMA therapy (OR 0.486, p<0.001). There was no significant difference in follow-up duration between the DAC and AZA groups. Over 50% of HMA-treated patients received 4 or more treatment cycles, with no significant difference between DAC (n=37) and AZA (n=60). Mean (SD) days from MDS diagnosis to first treatment was 93.7 (101.4) for DAC vs. 50.8 (73.4) for AZA (p=0.03). Median treatment days per cycle were 4.86 for DAC and 5.00 for AZA (p>0.05). Mean (SD) days to discontinuation of RBC/PLT transfusion was 15.8 (48.3) for DAC and 70.1 (136.1) for AZA (p<0.05). The RBC/PLT transfusion rate was lower for DAC than for AZA (0.06 vs 0.17 per month, p<0.05). Poisson regression found a significantly lower likelihood of RBC/PLT transfusion in the DAC group (OR=0.206, p<0.05). Use of ESA did not differ between treatments (p>0.05). Discussion: Only a small portion of MDS patients receive HMA treatments, with females less likely to receive drug therapy. Initiation of decitabine occurs later than azacitadine after MDS diagnosis for unclear reasons. Decitabine is associated with lower rates of RBC/PLT transfusion and shorter time to discontinuation of transfusions, consistent with a prompt time to clinical response. Further research is needed to clarify optimal initiation timing for HMA treatment to maximize therapeutic benefits. Disclosures: Hatoum: Eisai Inc.: Research Funding. Lin:Eisai Inc.: Research Funding. Buchner:Eisai Inc.: Employment. Kim:Eisai Inc.: Employment.

High-Dose Methotrexate In The Treatment Of Primary Testicular Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5108-5108 ◽  
Author(s):  
Marika Reinius ◽  
Saif S Ahmad ◽  
Charles Crawley ◽  
Michael V Williams ◽  
Jennie Wimperis ◽  
...  
Keyword(s):  
Systemic Disease ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Contralateral Testis ◽  
Cns Relapse ◽  
Testicular Lymphoma ◽  
Grade 3 ◽  
To Receive ◽  
Primary Testicular Lymphoma

Abstract Background Primary testicular lymphoma (PTL) presents in most cases, histologically, as a diffuse large B-cell lymphoma. PTL has a propensity for metastases to the central nervous system (CNS) cited as 20% at 5 years. Bilateral testicular involvement is seen in 35% of cases. Treatment commonly consists of orchidectomy followed by Rituximab- cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP), intrathecal methotrexate (IT-MTX) and prophylactic radiotherapy to the contralateral testis. Administration of systemic high-dose MTX (HD-MTX), at 3 g/m2, has been proposed as an approach to improve CNS parenchymal penetration and may prevent the need for scrotal irradiation. From 2005 within the Anglia Cancer Network, HD-MTX was incorporated into standard treatment for patients with PTL, who were fit enough to receive high dose therapy. Here we report outcomes from the 2 largest lymphoma centres within the network. Method A retrospective review was carried out using medical records of patients with PTL treated with HD-MTX at Cambridge University Hospitals (CUH) and Norfolk and Norwich University Hospital (NNUH), UK, from 2005 onwards. Histological diagnoses were made via orchidectomy or testicular biopsy. Factors reviewed included: age, stage, ECOG performance status, presence of B symptoms and IPI score at diagnosis, treatment regimen, grade 3/4 toxicity and clinical outcome. Stage IV disease was excluded as it cannot be distinguished from a non-testicular primary. Results 10 patients were identified who met the search criteria. 6 were treated at CUH and 4 at NNUH. Median age at diagnosis was 61.5 (49-71). All patients presented with scrotal swelling and 30% had bilateral tumours. ECOG PS was 0 (90%) and 1 (10%). 80% had stage IE disease and 20% stage IIE (paraaortic). Median IPI was 1. Patients were planned to receive 6 cycles of R-CHOP21 with 3-6 cycles IT-MTX with 3 cycles HD-MTX (3 g/m2) administered between or after R-CHOP21. Patients at NNUH only also received radiotherapy at 30 Gy in 15 fractions to the contralateral testis +/- PA nodes if stage IIE disease. One NNUH patient did not receive IT-MTX and one CUH patient only received 2 cycles HD-MTX for logistical reasons. No grade 3 or 4 toxicities were noted. At time of submission with a median follow-up of 4.27 years, only 1 patient has relapsed within the bone marrow. He died of systemic disease but was not shown to have CNS relapse. One patient died of a non-PTL related cause. 8 patients remain in ongoing first remission. No cases of CNS or testicular relapse have been noted in our 10 patients including the 6 patients who did not receive scrotal irradiation. One patient at CUH with bilateral disease was diagnosed on biopsies alone. He underwent unilateral orchidectomy after completing systemic treatment demonstrating a complete response, despite no radiotherapy. He declined a second orchidectomy and remains relapse free at 5.91 years follow-up. Conclusion Treating PTL with HD-MTX, IT-MTX and R-CHOP has shown encouraging clinical outcomes in terms of treatment tolerability and disease-free survival at a median follow-up of 4.27 years. Accepting the small numbers, the absence of CNS relapse with this follow-up suggests prophylactic efficacy of HD-MTX. The finding that disease was eliminated in an in situ testis following treatment is also significant, given the standard practice of contralateral testicular irradiation. These results highlight the need for further prospective research to determine the role of HD-MTX in the management of PTL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Outcome in patients with differentiated thyroid cancer with negative diagnostic whole-body scanning and detectable stimulated thyroglobulin

2003 ◽  
pp. 589-596 ◽  
Author(s):  
KM van Tol ◽  
PL Jager ◽  
EG de Vries ◽  
DA Piers ◽  
HM Boezen ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Tumor Location ◽  
Differentiated Thyroid Carcinoma ◽  
Post Treatment ◽  
Whole Body ◽  
High Dose ◽  
Serum Thyroglobulin ◽  
Thyroid Hormone Withdrawal ◽  
Iodine Treatment

BACKGROUND: Management of patients with differentiated thyroid carcinoma with negative diagnostic radioiodide scanning and increased serum thyroglobulin (Tg) concentrations is a widely debated problem. High-dose iodine-131 treatment of patients who have a negative (131)I diagnostic whole-body scan (WBS) is advocated. However, the therapeutic benefit of this "blind" treatment is not clear. OBJECTIVE: To investigate the course of serum Tg during thyroid hormone suppression therapy (Tg-on) and clinical outcome in patients with negative diagnostic (131)I scanning and increased serum Tg concentrations during thyroid hormone withdrawal (Tg-off), after treatment with high-dose (131)I. DESIGN: Retrospective single-center study. METHODS: Fifty-six patients were treated with a blind therapeutic dose of 150 mCi (131)I. Median follow-up from this treatment until the end of observation was 4.2 Years (range 0.5-13.5 Years). RESULTS: The post-treatment WBS revealed (131)I uptake in 28 patients, but none in the remaining 28 patients. In this study the Tg-on values did not change after treatment in either the positive or the negative post-treatment WBS group. During follow-up, 18 of the 28 patients with a positive post-treatment WBS achieved complete remission, compared with 10 of the 28 patients with a negative post-treatment WBS. Nine patients in the negative group died, but no patients died in the positive post-treatment group (P=0.001). CONCLUSIONS: High-dose iodine treatment in diagnostically negative patients who have a negative post-treatment scan seems to confer no additional value for tumor reduction and survival. In patients with a positive post-treatment scan, high-dose iodine treatment can be used as a diagnostic tool to identify tumor location, and a therapeutic effect may be present in individual cases.

scholarly journals DESTINATION: a phase 3, multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the long-term safety and tolerability of tezepelumab in adults and adolescents with severe, uncontrolled asthma

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Sandhia Ponnarambil ◽  
John Downie ◽  
Karin Bowen ◽  
Åsa Hellqvist ◽  
...  
Keyword(s):  
High Dose ◽  
Treatment Cessation ◽  
Uncontrolled Asthma ◽  
Phase 3 ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Long Term Treatment ◽  
To Receive

Abstract Background Tezepelumab is a human monoclonal antibody that blocks the activity of the epithelial cytokine thymic stromal lymphopoietin. The efficacy, safety and oral corticosteroid-sparing potential of tezepelumab are being investigated in two ongoing, phase 3, randomized, double-blind, placebo-controlled studies (NAVIGATOR [NCT03347279] and SOURCE [NCT03406078]). DESTINATION (NCT03706079) is a long-term extension (LTE) of these studies. Methods DESTINATION is a randomized, double-blind, placebo-controlled LTE study in adults (18–80 years old) and adolescents (12–17 years old) with severe, uncontrolled asthma who are receiving treatment with medium- or high-dose inhaled corticosteroids plus at least one additional controller medication with or without oral corticosteroids. The study population will comprise patients who complete the 52- and 48-week NAVIGATOR and SOURCE studies, respectively. Patients who were randomized to receive tezepelumab 210 mg every 4 weeks (Q4W) in either predecessor study will continue to receive this regimen for 1 year; those who were previously randomized to receive placebo will be re-randomized (1:1) to receive either tezepelumab 210 mg Q4W or placebo for 1 year. Patients will receive their prescribed controller medications throughout DESTINATION and study physicians will have the opportunity to down- or up-titrate dosage of these medications, if appropriate. The primary objective is to evaluate the long-term safety and tolerability of tezepelumab over 104 weeks (inclusive of the treatment period of either predecessor study). The secondary objective is to assess the long-term effect of tezepelumab on asthma exacerbations. Patients recruited from SOURCE will be followed up post-treatment for 12 weeks. Patients recruited from NAVIGATOR who complete 100 weeks of tezepelumab treatment will be eligible for either 12 weeks of follow-up or a 36-week extended follow-up during which the clinical benefit of tezepelumab after treatment cessation will be investigated. Discussion DESTINATION will evaluate the long-term safety, tolerability and efficacy of tezepelumab versus placebo with continued dosing for up to 2 years. DESTINATION will also evaluate the clinical effect of tezepelumab after treatment cessation. This LTE study aims to elucidate the long-term safety implications of receiving tezepelumab and to assess its potential long-term treatment benefits in patients with severe, uncontrolled asthma. Trial registration NCT03706079 (ClinicalTrials.gov). Registered 15 October 2018.

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